ⓘ Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathi ..

                                     

ⓘ Acetazolamide

Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension, and heart failure. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out. It is taken by mouth or injection into a vein.

Common side effects include numbness, ringing in the ears, loss of appetite, vomiting, and sleepiness. It is not recommended in those with significant kidney problems, liver problems, or who are allergic to sulfonamides. Acetazolamide is in the diuretic and carbonic anhydrase inhibitor families of medication. It works by decreasing the amount of hydrogen ions and bicarbonate in the body.

Acetazolamide came into medical use in 1952. It is on the World Health Organizations List of Essential Medicines, the safest and most effective medicines needed in a health system. Acetazolamide is available as a generic medication. The wholesale cost in the developing world is about US$1.40–16.93 per month. In the United States the wholesale cost is about US$125.34 per month.

                                     

1. Medical uses

It is used in the treatment of glaucoma, drug-induced edema, heart failure-induced edema, epilepsy and in reducing intraocular pressure after surgery. It has also been used in the treatment of altitude sickness, Menieres disease, increased intracranial pressure and neuromuscular disorders.

In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy. It has been demonstrated in drug trials to relieve symptoms associated with dural ectasia in individuals with Marfans Syndrome. A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central as opposed to obstructive sleep apnea.

It has also been used to prevent methotrexate-induced kidney damage by alkalinalizing the urine, hence speeding up methotrexate excretion by increasing its solubility in urine. There is some evidence to support its use to prevent hemiplegic migraine.

                                     

1.1. Medical uses High altitude sickness

In the treatment of mountain sickness, acetazolamide forces the kidneys to excrete bicarbonate, the conjugate base of carbonic acid. By increasing the amount of bicarbonate excreted in the urine, the blood becomes more acidic. As the body equates acidity of the blood to its CO 2 concentration, artificially acidifying the blood fools the body into thinking it has an excess of CO 2, and it excretes this imaginary excess CO 2 by deeper and faster breathing, which in turn increases the amount of oxygen in the blood. Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up part of the acclimatization process which in turn helps to relieve symptoms. Acetazolamide is still effective if started early in the course of mountain sickness. As prevention, it is started one day before travel to altitude and continued for the first 2 days at altitude.

                                     

1.2. Medical uses Pregnancy and lactation

Acetazolamide is pregnancy category B3 in Australia, which means that studies in rats, mice and rabbits in which acetazolamide was given intravenously or orally caused an increased risk of fetal malformations, including defects of the limbs. Despite this, there is insufficient evidence from studies in humans to either support or discount this evidence.

Limited data are available on the effects of nursing mothers taking acetazolamide. Therapeutic doses create low levels in breast milk and are not expected to cause problems in infants.

                                     

2. Side effects

Common adverse effects of acetazolamide include the following: paraesthesia, fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black feces, polyuria, kidney stones, metabolic acidosis and electrolyte changes hypokalemia, hyponatremia. Whereas less common adverse effects include Stevens–Johnson syndrome, anaphylaxis and blood dyscrasias.

                                     

2.1. Side effects Contraindications

Contraindications include:

  • Hypersensitivity to acetazolamide or other sulfonamides.
  • Adrenal insufficiency
  • Hyperchloremic acidosis
  • Impaired kidney function
  • Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance.
  • Hyponatremia low blood sodium
  • Hypokalemia low blood potassium
                                     

2.2. Side effects Interactions

It is possible that it might interact with:

  • Sodium bicarbonate, potential for kidney stone formation.
  • Anticoagulants, cardiac glycosides, may have their effects potentiated by acetazolamide.
  • Other carbonic anhydrase inhibitors - potential for additive inhibitory effects on carbonic anhydrase and hence potential for toxicity.
  • Hypoglycemics, acetazolamide can both increase or decrease blood glucose levels.
  • Methenamine compounds, reduces the urinary excretion of methenamines.
  • Phenytoin, reduces phenytoin excretion, hence increasing the potential for toxicity.
  • Primidone, reduces plasma levels of primidone. Hence reducing anticonvulsant effect.
  • Ciclosporin, may increase plasma levels of ciclosporin.
  • Salicylates, potential for severe toxicity.
  • Amphetamines, because it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines.
  • Quinidine, reduces urinary excretion of quinidine, hence increasing the potential for toxicity.
  • Lithium, increases excretion, hence reducing therapeutic effect.
  • Antifolates such as trimethoprim, methotrexate, pemetrexed and raltitrexed.


                                     

3. Mechanism of action

Acetazolamide is a carbonic anhydrase inhibitor, hence causing the accumulation of carbonic acid. Carbonic anhydrase is an enzyme found in red blood cells and many other tissues that catalyses the following reaction:

H 2 CO 3 ⇌ H 2 O + CO 2

hence lowering blood pH, by means of the following reaction that carbonic acid undergoes:

H 2 CO 3 ⇌ HCO 3 − + H +

which has a pK a of 6.3.

The mechanism of diuresis involves the proximal tubule of the kidney. The enzyme carbonic anhydrase is found here, allowing the reabsorption of bicarbonate, sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, lowering blood pressure, intracranial pressure, and intraocular pressure. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation with deep respiration Kussmaul respiration, increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.

In the eye this results in a reduction in aqueous humour.

Bicarbonate HCO 3 − has a pK a of 10.3 with carbonate CO 3 2−, far further from physiologic pH 7.35–7.45, and so it is more likely to accept a proton than to donate one, but it is also far less likely for it to do either, thus bicarbonate will be the major species at physiological pH.

Under normal conditions in the proximal convoluted tubule of the kidney, most of the carbonic acid H 2 CO 3 produced intracellularly by the action of carbonic anhydrase quickly dissociates in the cell to bicarbonate HCO 3 − and an H + ion a proton, as previously mentioned. The bicarbonate HCO 3 − exits at the basal portion of the cell via sodium Na + symport and chloride Cl − antiport and re-enters circulation, where it may accept a proton if blood pH decreases, thus acting as a weak, basic buffer. The remaining H + left over from the intracellular production of carbonic acid H 2 CO 3 exits the apical urinary lumen portion of the cell by Na + antiport, acidifying the urine. There, it may join with another bicarbonate HCO 3 − that dissociated from its H + in the lumen of the urinary space only after exiting the proximal convoluted kidney cells/glomerulus as carbonic acid H 2 CO 3 because bicarbonate HCO 3 − itself can not diffuse across the cell membrane in its polar state. This will replenish carbonic acid H 2 CO 3 so that it then may be reabsorbed into the cell as itself or CO 2 and H 2 O produced via a luminal carbonic anhydrase. As a result of this whole process, there is a greater net balance of H + in the urinary lumen than bicarbonate HCO 3 −, and so this space is more acidic than physiologic pH. Thus, there is an increased likelihood that any bicarbonate HCO 3 − that was left over in the lumen diffuses back into the cell as carbonic acid, CO 2, or H 2 O.

In short, under normal conditions, the net effect of carbonic anhydrase in the urinary lumen and cells of the proximal convoluted tubule is to acidify the urine and transport bicarbonate HCO 3 − into the body. Another effect is excretion of Cl − as it is needed to maintain electroneutrality in the lumen, as well as the reabsorption of Na + into the body.

Thus, by disrupting this process with acetazolamide, urinary Na + and bicarbonate HCO 3 − are increased, and urinary H + and Cl − are decreased. Inversely, serum Na + and bicarbonate HCO 3 − are decreased, and serum H + and Cl − are increased. H 2 O generally follows sodium, and so this is how the clinical diuretic effect is achieved, which reduces blood volume and thus preload on the heart to improve contractility and reduce blood pressure, or achieve other desired clinical effects of reduced blood volume such as reducing edema or intracranial pressure.



                                     
  • excretion of uric acid, they can be used in the treatment of gout. Acetazolamide is an inhibitor of carbonic anhydrase. It is used for glaucoma, epilepsy
  • altitude and sufficient fluids. Mild cases may be helped by ibuprofen, acetazolamide or dexamethasone. Severe cases may benefit from oxygen therapy and
  • disorder. Different medication has been tried as treatment, notably acetazolamide valproate, lamotrigine, topiramate, and furosemide. Haas, David C.
  • doping at the 2018 Winter Olympics after he was found to have been using acetazolamide Saito, Kei. 齋藤慧 Facebook in Japanese Retrieved 5 March 2018.
  • Texas Revolution Diureticum - Holzinger, another name for the molecule acetazolamide Holzinger class patrol vessel, an offshore patrol vessels class in use
  • achieved in August 2003 in Tula. In 2007 Konovalov was found guilty of acetazolamide doping. The sample was delivered on 17 December 2006 in an in - competition
  • reanalysis which resulted in a positive test for the prohibited substance Acetazolamide Barrios sold her Olympic silver medal on auction site, eBay, for unknown
  • hemiplegic migraine or spinocerebellar ataxia. Some patients respond to acetazolamide though others do not. Typically, episodic ataxia presents as bouts of
  • the 2017 Tour of Qinghai Lake, Antonio Santoro tested positive for Acetazolamide and was banned for six months. 2014 Stage 3b Sibiu Cycling Tour, Marco
  • H secretion Long - term use of a carbonic anhydrase inhibitor such as acetazolamide Other causes Ingestion of ammonium chloride, hydrochloric acid, or other
  • medalist Yarelis Barrios and disqualified her for having the masking agent acetazolamide in her sample. She was stripped of her medal. If the IOC reallocates
  • Medications that may be used to treat the condition include lamotrigine, acetazolamide or verapamil. These do not always result in benefits, however. Some
  • acidosis Hyperalimentation e.g. from TPN containing ammonium chloride Acetazolamide and other carbonic anhydrase inhibitors Renal tubular acidosis Diarrhea: